- Discovery of Salidroside-Derivated Glycoside Analogues as Novel Angiogenesis Agents to Treat Diabetic Hind Limb Ischemia
-
Therapeutic angiogenesis is a potential therapeutic strategy for hind limb ischemia (HLI); however, currently, there are no small-molecule drugs capable of inducing it at the clinical level. Activating the hypoxia-inducible factor-1 (HIF-1) pathway in skeletal muscle induces the secretion of angiogenic factors and thus is an attractive therapeutic angiogenesis strategy. Using salidroside, a natural glycosidic compound as a lead, we performed a structure-activity relationship (SAR) study for developing a more effective and druggable angiogenesis agent. We found a novel glycoside scaffold compound (C-30) with better efficacy than salidroside in enhancing the accumulation of the HIF-1α protein and stimulating the paracrine functions of skeletal muscle cells. This in turn significantly increased the angiogenic potential of vascular endothelial and smooth muscle cells and, subsequently, induced the formation of mature, functional blood vessels in diabetic and nondiabetic HLI mice. Together, this study offers a novel, promising small-molecule-based therapeutic strategy for treating HLI.
- Liu, Caiping,Han, Jingxuan,Marcelina, Olivia,Nugrahaningrum, Dyah Ari,Huang, Song,Zou, Meijuan,Wang, Guixue,Miyagishi, Makoto,He, Yun,Wu, Shourong,Kasim, Vivi
-
supporting information
p. 135 - 162
(2022/01/14)
-
- A general approach to C-Acyl glycosides via palladium/copper Co-catalyzed coupling reaction of glycosyl carbothioates and arylboronic acids
-
A general and efficient approach to the synthesis of various C-acyl glycosides has been developed via Pd2(dba)3/CuTC co-catalyzed cross-coupling reaction of glycosyl carbothioates with arylboronic acids. The reaction showed a broad s
- Wang, Li-Na,Niu, You-Hong,Cai, Qing-Hui,Li, Qin,Ye, Xin-Shan
-
supporting information
(2021/02/03)
-
- An efficient and practical preparation of a potent low-affinity na+-dependent glucose cotransporter (SGLT2) inhibitor, sergliflozin etabonate
-
The development of an efficient and practical process for the preparation of Sergliflozin etabonate (1), a prodrug of a novel selective low-affinity Na+-dependent glucose cotransporter (SGLT2) inhibitor, Sergliflozin (2), is described. Its development required a suitable process for large-scale manufacturing. We established a chromatography-free approach for 2-[(4-methoxyphenyl)methyl]phenol (5), the efficient O-glycosylation of 5 with penta-O-acetyl-β-D-glucopyranose (7) without using a trichloroacetimidate intermediate (9), and efficient reaction conditions to introduce an ethoxycarbonyl group onto the primary alcohol of 2 with high selectivity. This process provided 1 with a 45% overall yield from anisole (10).
- Kobayashi, Masahiro,Isawa, Hidetoshi,Sonehara, Junichi,Kubota, Minoru
-
p. 1599 - 1613
(2016/10/12)
-
- Catalytic Tandem and One-Pot Dehydrogenation-Alkylation and -Insertion Reactions of Saturated Hydrocarbons with Alcohols and Alkenes
-
The ruthenium-hydride catalyst has been successfully used for the tandem sp3 C-H dehydrogenation-alkylation reaction of saturated hydrocarbon substrates with alcohols to form the alkyl-substituted alkene and arene products. The analogous one-pot dehydrogenation-insertion of saturated ketones with alkenes and dienes directly yielded synthetically useful 2-alkylphenol and benzopyran products in a highly regio- and stereoselective manner without forming any wasteful byproducts. (Chemical Equation Presented).
- Kim, Junghwa,Pannilawithana, Nuwan,Yi, Chae S.
-
p. 8395 - 8398
(2016/12/16)
-
- Design, syntheses, and SAR studies of carbocyclic analogues of sergliflozin as potent sodium-dependent glucose cotransporter 2 inhibitors
-
Combating diabetes: A small-molecule carbohydrate mimic, pseudo-sergliflozin, was synthesized effectively by a regio- and stereoselective allylic substitution reaction. It was found to be a potent and selective inhibitor of a transporter protein - sodium-dependent glucose cotransporter 2 (SGLT2) - which is responsible for glucose reabsorption in the human body. It could be a lead compound for further development into an antidiabetic agent. Copyright
- Shing, Tony K. M.,Ng, Wai-Lung,Chan, Judy Y.-W.,Lau, Clara B.-S.
-
supporting information
p. 8401 - 8405
(2013/09/02)
-
- FAMILY OF ARYL, HETEROARYL, O-ARYL AND O-HETEROARYL CARBASUGARS
-
The present invention relates to a compound of the following formula (I): as well as its process of preparation, pharmaceutical and cosmetics composition comprising it and use thereof, notably as an inhibitor of the sodium-dependent glucose co-transporter, such as SGLTl, SGLT2 and SGLT3, in particular in the treatment or prevention of diabetes, and more particularly type-II diabetes, diabetes-related complications, such as arthritis of the lower extremities, cardiac infarction, renal insufficiency, neuropathy or blindness, hyperglycemia, hyperinsulinemia, obesity, hypertriglyceridemia, X syndrome and arteriosclerosis, as well as for its use as an anticancer, anti-infective, anti-viral, anti-thrombotic or anti- inflammatory drug, or for lightening, bleaching, depigmenting the skin, removing blemishes from the skin, particularly age spots and freckles, or preventing pigmentation of the skin.
- -
-
Page/Page column 59-60
(2012/12/13)
-
- METHOD FOR PRODUCING 2-BENZYLPHENOL COMPOUND
-
[Task] Provide a process for producing a 2-benzylphenol compound easily, efficiently and selectively. [Means for Achievement] A process for producing a 2-benzylphenol compound represented by the following general formula (2) (in the formula, R1, R2, R3 and R4 may be the same or different and are each independently hydrogen atom, alkyl group or the like; and R5, R6, R7, R8 and R9 may be the same or different and are each independently hydrogen atom, alkyl group or the like), characterized by reacting, in the presence of a dehydrogenating agent, a benzylidenecyclohexanone compound represented by the following general formula (1) (in the formula, R1, R2, R3, R4, R5, R6, R7, R8 and R9 have the same definitions as given above). [Effect] A 2-benzylphenol compound substantially free from isomers can be produced from a benzylidenecyclohexanone compound (an easily obtainable raw material) selectively, efficiently and in a simple operation, under mild conditions without using any special reactor.
- -
-
-
- METHOD FOR PRODUCING 2-BENZYLPHENOL COMPOUND
-
Disclosed is a simple method for efficiently and selectively producing a 2-benzylphenol compound. Specifically disclosed is a method for producing a 2-benzylphenol compound represented by the following general formula (2): (wherein R1, R2, R3, R4, R5, R6, R7, R8 and R9 represent the same as defined in the general formula (1) below) which is characterized by reacting a benzylidenecyclohexane compound represented by the following general formula (1): (wherein R1, R2, R3 and R4 may be the same or different and respectively represent a hydrogen atom, an alkyl group or the like; and R5, R6, R7, R8 and R9 may be the same or different and respectively represent a hydrogen atom, an alkyl group or the like) in the presence of a dehydrogenation agent. Consequently, a 2-benzylphenol compound substantially containing no isomers can be produced selectively and efficiently under mild conditions by a simple procedure using an easily-available benzylidenecyclohexane compound as the raw material without requiring a special reaction equipment.
- -
-
Page/Page column 34
(2008/06/13)
-
- Novel aromatic fluoroglycoside derivatives, medicaments containing these compounds, and the use thereof
-
Novel aromatic fluoroglycoside derivatives, medicaments containing these compounds, and the use thereof. The invention relates to substituted aromatic fluoroglycoside derivatives of the formula I in which the radicals have the stated meanings, and their p
- -
-
Page/Page column 24
(2008/06/13)
-
- The reactivity of o-hydroxybenzyl alcohol and derivatives in solution at elevated temperatures
-
The reactivity of o-hydroxybenzyl alcohol (o-HBA, 1), as a model compound for lignin, has been studied in various solvents between 390 and 560 K. Both in polar and apolar solvents the benzylic cation is the reactive intermediate. In alcoholic solvents, the benzylic cation reacts with the solvent to give the corresponding ethers. Relative reaction rates have been determined for different alcohols; a factor of 14 is encountered between the most (methanol) and least (tert-butyl alcohol) reactive ones. The etherification is reversible, in contrast to the electrophilic aromatic substitution with phenol and anisole, for which k(PhOH) = 1 X 105 M-1 s- 1 and k(anisole) = 1 x 104 M-1 s-1, at 424 K. In apolar hydroaromatic solvents, 7H-benz[de]anthracene, 9,10-dihydroanthracene, and 9,10- dihydrophenanthrene, the formation of o-cresol proceeds via hydride transfer from the solvent to the benzylic cation; rate constants at 555 K are 2 x 106, 5 x 104, and 5 x 103 M-1 s-1, respectively.
- Dorrestijn, Edwin,Kranenburg, Marieke,Ciriano, Maria Victoria,Mulder, Peter
-
p. 3012 - 3018
(2007/10/03)
-
- Reactions of 2-phenyl-4H-1,3,2-benzodioxaborin, a stable ortho-quinone methide precursor
-
Thermolysis of 1-phenyl-4H-1,3,2-benzodioxaborins generated the corresponding ortho-quinone methides, which were found to undergo intermolecular cycloaddition reactions with ethyl vinyl ether, dihydropyran, β-methylstyrene, cyclohexene, and 1-ethoxy-1-trimethylsiloxy-1-propenes to give various substituted chromans.Intramolecular trapping of the quinone methides with an olefin led to the syntheses of several analogs of tetrahydrocannabinols. ortho-Quinone methides, generated by treatment of the 2-phenyl-4H-1,3,2-benzodioxaborins with a Lewis acid, react with various nucleophiles to give the corresponding 1,4-addition products.Thus, alkyl and aryl thiols, alcohols, amine, hydride, allyl trimethylsilane, acetophenone, and diethyl malonate as well as some aryl compounds react with the quinone methide to give various 2-substituted phenols.Intramolecular reaction of the quinone methide with an aryl group led to the preparation of some 4-phenylchromans and tetralins.
- Chambers, Jeffrey D.,Crawford, Jason,Williams, Haydn W. R.,Dufresne, Claude,Scheigetz, John,et al.
-
p. 1717 - 1732
(2007/10/02)
-
- Deprotection of carboxylic esters assisted by hydrogen bonding network in phenolic media. Its application to β-lactam antibiotic syntheses
-
Deprotection of p-methoxybenzyl, diphenylmethyl, and tert-butyl ester groups, which is an essential step of β-lactam antibiotic synthesis, can be performed successfully by gentle heating in phenolic media.
- Tanaka, Hideo,Taniguchi, Masatoshi,Kameyama, Yutaka,Torii, Sigeru,Sasaoka, Michio,Shiroi, Takashi,Kikuchi, Ryo,Kawahara, Ichiro,Shimabayashi, Akihiro,Nagao, Sigemitsu
-
p. 6661 - 6662
(2007/10/02)
-
